Process for the production of 1-substituted-5(4H)-tetrazolinones

Abstract: 1-Substituted-5(4H)-tetrazolinones of the formula (I) wherein R is alkyl, haloalkyl, cycloalkyl, optionally substituted phenyl or aralkyl, can be obtained in very good yields by reacting, in a polar solvent, an isocyanate of the formula R-NCO (II) with sodium azide (NaN₃) in a molar ratio of 1 : 1 and in the presence of aluminium chloride (AlCl₃), followed by the addition of water and a mineral acid in excess.

Description: The present invention relates to a process for the production of 1-substituted-5(4H)-tetrazolinones. Tetrazolinone derivatives can be employed as industrially useful active substances such as medicines, agricultural chemicals, etc., for example, as disclosed in Japanese Patent Application Publication No. Hei-2-24272, for example. For producing 1-substituted-5(4H)-tetrazolinones, starting materials for the above-mentioned tetrazolinone derivatives, J. Am. Chem. Soc., vol. 81, p.p. 3076 - 3079 (1959) discloses a process wherein an isocyanate selected from a number of isocyanate derivatives is reacted with sodium azide in tetrahydrofurane and in the presence of aluminum chloride. However, that process has such disadvantages that, to obtain a good yield, use must be made of as much as three equivalents of sodium azide per equivalent of isocyanate as well as of tetrahydrofurane as the solvent. That is a very expensive compound, so it is not attractive in view of industrial and economical considerations to employ that process. Further, a process is disclosed in J. Org. Chem. vol. 45, p.p. 5130 - 5136 (1980), wherein an isocyanate selected from a number of isocyanate derivatives is reacted with trimethylsilyl azide,but this process has also been found to be inappropriate industrially because trimethylsilyl azide is an expensive material and about two equivalents must be used per equivalent of isocyanate to obtain a satisfactory yield, further requiring such severe reaction condition as refluxing under heating in the absence of solvent. To solve these problems, there has now been found a process for the production of 1-substituted-5(4H)-tetrazolinones of the general formula (I) wherein R is C 1-6 alkyl, C 1-4 haloalkyl, C 3-8 cycloalkyl, benzyl, phenethyl, or phenyl optionally substituted by C 1-4 alkyl, halogen, nitro, cyano, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, C 1-4 alkylthio, phenoxy, C 1-4 haloalkoxy or C 1-4 haloalkylthio, which comprises reacting, in a polar solvent selected from the group comprising N,N-dimethyl formamide, N,N-dimethyl acetamide, N-methylpyrrolidone and 1,3-dimethylimidazolinone, an isocyanate of the formula (II) RNCO wherein R has the same meaning as mentioned above, with sodium azide in an equimolar ratio (1:1) and in the presence of aluminum chloride, followed by addition of water and a mineral acid in excess. According to this process where use is made, as a polar solvent, of N,N-dimethyl formamide, for example, it has been unpredictably found that the desired 1-substituted-5(4H)-tetrazolinones are obtained in good yield and, as a result, this process is suitable for use on industrial scale. The above terms "halo..." and "halogen" include fluorine, chlorine and bromine. The above expression "phenyl optionally substituted" includes both "unsubstituted phenyl" and "substituted phenyl". When, for example, 2-chlorophenyl isocyanate and sodium azide are employed as starting materials, the reaction is illustrated by the following equation: Representative isocyanates (II) include: ethylisocyanate, n-propylisocyanate, t-butylisocyanate, 2-chloroethylisocyanate, 3-chloropropylisocyanate, cyclopentylisocyanate, cyclohexylisocyanate, benzylisocyanate, phenylisocyanate, 2-chlorophenylisocyanate, 2-chloro-6-methylphenylisocyanate, 2-trifluoromethylphenylisocyanate, o-tolylisocyanate, 2-nitrophenylisocyanate, 2-cyanophenylisocyanate, 2-methoxyphenylisocyante, 2-trifluoromethoxyphenylisocyanate, 2-trifluoromethylthiophenyl isocyanate, 2-bromophenylisocyanate, 2-methylthiophenylisocyanate, 2-ethylphenylisocyanate, 2-isopropylphenylisocyanate, 2,6-dimethylphenylisocyanate, 2-ethyl-6-methylphenylisocyanate, 2-fluorophenylisocyanate, 2,6-diethylphenylisocyanate, 2,6-dichlorophenylisocyanate, 2,4-dichlorophenylisocyanate, 2,5-dichlorophenylisocyanate, 2,4,6-trichlorophenylisocyanate, 2,4,6-trimethylphenylisocyanate, 4-bromo-2,6-dimethylphenylisocyanate, 2-phenoxyphenylisocyanate, phenethylisocyanate, 3-chloro-4-trifluoromethylphenylisocyanate, 2-chloro-4-trifluoromethylphenylisocyanate. Representative polar solvents include N,N-dimethyl formamide, N,N-dimethyl acetamide, N-methylpyrrolidone and 1,3-dimethylimidazolinone, preferably N,N-dimethyl formamide. In carrying out the process with N,N-dimethyl formamide as polar solvent, for example, one mol of an isocyanate of the general formula (II) is reacted with 1 mol of sodium azide and 0.005 to 1.5 mols of aluminum chloride, preferably catalytic amount of 0.01 to 1.0 mol, at a reaction temperature from about 0° to about 200°C, preferably from about 25° to about 150°C, and normal pressure for about 2 to about 24 hours, preferably about 3 to about 10 hours. The production process according to the present invention will be explained hereinbelow by way of examples. Examples Synthesis Example 1 Anhydrous aluminium chloride (1.5 g) was added to N,N-dimethylformamide (20 ml) under ice cooling and the resulting mixture was stirred for fifteen minutes. To the mixture was added sodium azide (0.65 g), followed by a 15 minute-stirring, addition of 2-chlorophenylisocyanate (1.53 g) thereto and heating at 70 to 75°C for three hours in that order. After cooling, the reaction mixture was added with stirring to a mixture of sodium nitrite (1 g), water (200 ml) and ice (100 g) and the resulting mixture was acidified with a 10% hydrochloric acid (until a potassium iodide starch paper became discoloured), followed by extraction with ethyl acetate. The thus obtained ethyl acetate layer was washed with water, dried over sodium sulfate and evaporated under reduced pressure. The resulting residue was purified by flash column chromatography (eluent: hexane:ethyl acetate = 2:1) to obtain the desired 1-(2-chlorophenyl)-5(4H)-tetrazolinone (1.8 g) having a m.p. in the range of from 124.5° to 125.5°C in a yield of 92% of theory. Synthesis Example 2 Synthesis of 1-(2-chlorophenyl)-5(4H)-tetrazolinone by decreasing the amount of AlCl 3 : To a mixture composed of sodium azide (1.95 g) and N,N-dimethyl formamide (9 ml), anhydrous aluminium chloride (0.2 g) was added portionwise at ice bath temperature and under argon stream, and the resultant mixture was stirred at 70° to 75°C for 15 minutes. To the mixture was added 2-chlorophenyl isocyanate (4.71 g), and the whole was stirred at 70° to 75°C for 4 hours. The cooled reaction mixture was poured onto a mixture composed of sodium nitrite (NaNO 2 , 1 g), water (200 ml) and ice (50 g), and the whole was made acidic by addition of concentrated hydrochloric acid until a potassium iodide - starch reaction became positive. The resultant mixture was extracted with ethyl acetate (100 ml x 3). The combined ethyl acetate extract was washed with water, dried over anhydrous sodium sulfate and evaporated. The residue was subjected to silica gel flash column chromatography (eluent: n-hexane:ethyl acetate = 2:1) to give the desired 1-(2-chlorophenyl)-5(4H)-tetrazolinone (5.8 g) having a m.p. of 124.5 - 125.5 °C; yield: 98 % of theory. In analogous manner, there were obtained the following compounds shown in Table 1 in a yield of at least 90% of theory. Synthesis Examples 2 a-d The experiment according to the above Synthesis Example 2 was repeated four times, but the amount of anhydrous aluminium chloride (AlCl 3 ) was varied in each experiment. As shown in the following Table 2, the desired 1-(2-chlorophenyl)-5(4H)-tetrazolinone was obtained in acceptable high yields of 94 - 99 % of the theory: Example No. Amount of AlCl 3 (g) / Ratio Reaction Time (hours) Yield (%) 2 a 1.49 (0.37) 3 98 2 b 0.4 (0.1) 4 99 2 c 0.2 (0.05) 4 98 2 d 0.04 (0.01) 5 94 Note: The number under "Ratio" means the molar quantity of AlCl 3 per 1 mol of an isocyanate of the general formula (II). Comparative Synthesis Example 1 (by the process disclosed in J. Am. Chem. Soc., vol. 81, p. 3076, 1959) Anhydrous aluminum chloride (1.5 g) was added to tetrahydrofuran (30 ml) with ice bath cooling, followed by a fifteen minute-stirring, addition of sodium azide (1.95 g) and 2-chlorophenylisocyanate (1.53 g) thereto and a sixteen hour-refluxing under heating in that order. After cooling, the reaction mixture was added with stirring to a mixture of sodium nitrite (2 g), water (200 ml) and ice (100 g) and the resulting mixture was acidified with a 10% hydrochloric acid (until a potassium iodide starch paper became discoloured), followed by extraction with ethyl acetate. The thus obtained ethyl acetate layer was washed with water, dried over sodium sulfate and evaporated under reduced pressure. The resulting residue was purified through a flash column chromatography (eluent: hexane:ethyl acetete = 2:1) to obtain the desired 1-(2-chlorophenyl)-5(4H)-tetrazolinone (1.41 g) having a m.p. in the range of from 124.5 to 125.5°C in a yield of 72% of theory. Comparative Synthesis Example 2 (wherein an equi-molar reaction was carried out in the above-mentioned Comparative Synthesis Example 1) Anhydrous aluminum chloride (1.5 g) was added to tetrahydrofuran (30 ml) with ice bath cooling and the resulting mixture was stirred for fifteen minutes. To the mixture was added sodium azide (0.65 g) and 2-chlorophenylisocyanate (1.53 g), followed by a sixteen hour-refluxing. After cooling, the reaction mixture was added with stirring to a mixture of sodium nitrite (1 g), water (200 ml) and ice (100 g) and the resulting mixture was worked up in the same way as was employed in the foregoing Comparative Synthesis Example 1 to obtain the aimed 1-(2-chlorophenyl)-5(4H)-tetrazolinone (0.5 g) having a m.p. in the range of from 124.5 to 125.5°C in a yield of 25% of theory. Comparative Synthesis Example 3 (J. Org. Chem., vol. 45, p. 5230, 1980) A mixture of 2-chlorophenylisocyanate (7 g) and trimethylsilyl azide (7.9 g) was refluxed under heating for eight hours and then the mixture was evaporated to remove excess trimethylsilyl azide under reduced pressure distillation, followed by addition of methanol to the resulting residue. Thereafter, the methanol was distilled off under reduced pressure. The resulting residue was purified by flash column chromatography (eluent: hexane:ethyl acetate = 2:1) to obtain the desired 1-(2-chlorophenyl)-5(4H)-tetrazolinone (6.6 g) having a m.p. in the range of from 124° to 125.5°C, in a yield of 73% of theory. These show that the process according to the present invention is economical regarding materials employed, efficiency of solvents, and yields of the desired products, so that it can be practically carried out on an industrial scale.

Claims: A process for the preparation of a 1-substituted-5(4H)-tetrazolinone of the formula wherein R is C 1-6 alkyl, C 1-4 haloalkyl, C 3-8 cycloalkyl, benzyl, phenethyl, or phenyl optionally substituted by C 1-4 alkyl, halogen, nitro, cyano, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, C 1-4 alkylthio, phenoxy, C 1-4 haloalkoxy or C 1-4 haloalkylthio, which comprises reacting, in a polar solvent selected from the group comprising N,N-dimethyl formamide, N,N-dimethyl acetamide, N-methylpyrrolidone and 1,3-dimethylimidazolinone, an isocyanate of the formula (II) RNCO with sodium azide in an equimolar ratio (1:1) and in the presence of aluminum chloride, followed by addition of water and a mineral acid in excess. The process according to claim 1, wherein the polar solvent is N,N-dimethyl formamide. The process according to claim 2, wherein the amount of aluminium chloride is 0.005 to 1.5 mols per 1 mol of an isocyanate of the general formula (II). The process according to claim 2, wherein the amount of aluminium chloride is a catalytic amount of 0.01 to 1.0 mol per 1 mol of an isocyanate of the general formula (II).

Inventors: NARABU SHIN-ICHI, WATANABE YUKIYOSHI, YANAGI AKIHIKO, NARABU, SHIN-ICHI, WATANABE, YUKIYOSHI, YANAGI, AKIHIKO
Applicants: BAYER AGROCHEM KK, NIHON BAYER AGROCHEM K.K.
Application year: 1994
Main classification: C07D257
IPC codes: C07B61, B01J27, C07D257